S U M M A R Y1. The distribution of vitamin D and its metabolites in human tissues has been studied by the combined use of radioactive cholecalciferol and biological assays of antiricketic activity in tissue extracts.2. Injected radioactive cholecalciferol was cleared rapidly from the blood; unchanged vitamin D and various metabolites were detected subsequently in all tissues examined. The highest concentration of biological activity and radioactivity was in fat; this and, to a lesser extent, other tissues were shown to retain activity over a prolonged period of time.3. Adipose tissue and voluntary muscle are the principal sites of storage of vitamin D in man. Pre-existing tissue pools of vitamin D can, in some circumstances, invalidate the use of radioactively labelled cholecalciferol to trace the pattern of body distribution.4. Metabolically produced 25-hydroxycholecalciferol is also taken up from the blood into many tissues, probably by protein-binding. 5. Vitamin D is excreted in bile principally as more polar metabolites. Smaller amounts of cholecalciferol and 25-hydroxycholecalciferol are also excreted, and antiricketic activity has been demonstrated in the bile of individuals treated with vitamin D.6. An excess of cholecalciferol (or of 25-hydroxycholecalciferol) in the blood appears to be eliminated by the physicochemical processes of partition into tissue lipid and binding to tissue proteins. It is inferred tentatively that an increased concentration of vitamin D or of 25-hydroxycholecalciferol in the liver also causes an increased biliary excretion of these substances, and an increased hepatic formation and elimination of more polar metabolites of the vitamin.
S U M M A R Y1. The metabolism of radioactive vitamin D, has been studied in individuals low or deficient in vitamin D (group I) and in vitamin D treated subjects (group 11).2. In group I there was a smaller serum pool of vitamin D, turning over more rapidly than in group 11. The principal metabolite, peak IV, appeared more rapidly in the serum of group I ; the level of radioactivity attained in this and in the more polar metabolites, peak V and VI, was also higher than in group 11. Peak VI was the major radioactive component in serum after 100 days.3. Vitamin D treatment of individuals in group I converted the pattern of metabolism of radioactive vitamin D, to that characteristic of group 11. This effect was observed in healthy individuals and in patients with vitamin D deficiency or with chronic renal failure.4. The metabolic disposal of vitaminD entering the body appears to be determined by the state of vitamin D nutrition in the individual. Reported changes of vitamin D metabolism in diseases such as renal failure could be determined by the nutritional state of the patients studied rather than by the primary disease.
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